Targeted Intensification With ZBEAM and Autologous Stem Cell Transplantation in Patients With High-grade B-Cell Lymphoma

Targeted Intensification by a Preparative Regimen for Patients With High-grade B-Cell Lymphoma Utilizing Standard-dose Yttrium-90 Ibritumomab Tiuxetan (Zevalin) Radioimmunotherapy (RIT) Combined With High-dose BEAM Followed by Autologous Stem Cell Transplantation (ASCT)

The purpose of this study is to evaluate the efficacy and the safety of a preparative regimen utilizing standard-dose Yttrium-90 Ibritumomab Tiuxetan (Zevalin) radioimmunotherapy combined with high-dose BEAM followed by ASCT after first line treatment in patients aged from 18 to 65 years with poor prognosis CD 20 Diffuse Large B-Cell lymphoma

Inclusion Criteria:

• Aged from 18 to 65 years.
• Patient with pathologically proven, high grade B-cell Lymphoma CD 20 positive (WHO classification) :
• Diffuse large B cell lymphoma.
• Adverse prognostic factors IPI>1
• In Complete Remission, or partial response to first line treatment.
• Previously treated with chemotherapy regimen containing rituximab: R CHOP or R ACVBP
• Chemo-sensitive disease
• PET Scan prior transplant
• Eligible for autologous stem cell transplantation
• With a minimum life expectancy of 3 months.
• Negative HIV, HBV and HCV serologies (in the last 4 weeks except after vaccination).
• Having previously signed a written informed consent.

Exclusion Criteria:

• Histological transformation in diffuse large B cell lymphoma, any type of low grade lymphoma
• More than one line of treatment. Prior transplantation. Prior exposure to Zevalin
• Central nervous system or meningeal involvement by lymphoma.
• Contraindication to any drug contained in the chemotherapy regimen.
• Any serious active disease or co-morbid medical condition (according to the investigator's decision and information provided in the IDB).
• Poor renal function (creatinin level up to 2.5 maximum normal level) unless these abnormalities are related to the lymphoma.
• Poor hepatic function (total bilirubin level up to 30 micro mol/l, transaminases up to 2.5 maximum normal level) unless these abnormalities are related to the lymphoma.
• Poor bone marrow reserve as defined by neutrophils less than 1.5 G/l or platelets less than 100 G/l
• Large bone marrow irradiation more than 40percent.
• Bone marrow infiltration
• Lack of sufficient autologous hematopoietic stem cells for transplantation.
• Prior treatment with murine antibodies
• Known hypersensibility to murine antibodies or proteins
• Any history of cancer during the last 5 years, with the exception of non-melanoma skin tumors or stage 0 (in situ) cervical carcinoma.
• Treatment with any investigational drug within 30 days before planned first cycle of chemotherapy and during the study.
• Adult patient unable to give informed consent because of intellectual impairment.
• Pregnant or lactating women.